The long-term goal of this research is to identify neural mechanisms involved in the development and maintenance of nicotine use. Many believe that stressful life events can contribute to drug use in humans, and, recently, animal models have been developed for studying this phenomenon. Using these models, it has been shown that periodic exposure to unavoidable stressors can dramatically affect drug-seeking behavior, including relapse to drug-seeking in drug-free animals. Although this has been demonstrated in studies focused on various drugs of abuse, the effect of unavoidable stress on nicotine-seeking behavior has yet to be examined. Nicotine use has been reported to have declined over the last two decades, but it is still recognized as being the leading cause of preventable death in the United States. Unfortunately, the rate of relapse to nicotine use in those attempting to quit is very high, and a reason often cited for such relapse is exposure to stress. Thus, the specific aim of the present proposal is to determine if exposure to unavoidable stress will reinstate nicotine-seeking behavior in rats (male and female) experienced at nicotine self-administration, but then subjected to several days of nicotine abstinence. It is hypothesized that exposure to stress will reinstate extinguished nicotine-seeking behavior. If so, the results of the proposed experiment will be submitted as part of an R01 to study the neural mediation of this effect.